Fig. 4: IL-23→IL-10 cytokine adaptors mimic effects of IL-10.

a Model comparing natural IL-23 signaling through IL-23R and IL-12Rbβ1 (left, PDB ID: 6XDQ) vs. signaling through IL-23→IL-10 cytokine adaptors (right) which dimerize IL-10Rα and IL-10Rβ. Model of IL-23→IL-10 adaptors is comprised of IL-23p19 binder VHH 37D5 and IL-23p40 binder VHH 22E11 and IL-23p19 (PBD ID: 4GRW) overlaid with structures of IL-10 receptor complex (PDB ID: 6X93). b Cartoon representation of IL-23→IL-10 cytokine adaptor design. c, d IL-23→IL-10 adaptors induce a pSTAT3 signal in THP-1 cells similar to IL-10. c Dose–response curves for phospho-STAT3 in THP-1 cell line stimulated for 20 min with human IL-10, a supermonomeric version of IL-10, or IL-23 with equimolar IL-23→IL-10 cytokine adaptors. Data plotted as mean phospho-STAT3 mean fluorescence intensity, n = 2, N = 3. d Normalized pSTAT3 response in THP-1 cells stimulated with 10 nM WT IL-10, a supermonomeric variant of IL-10 (M), a monomeric dominant negative mutant of IL-10 (DN), IL-23, or IL-23 with the IL-23 → IL-10 adaptors. n = 2, N = 3. Data are plotted as mean ± SD. e–g IL-23→IL-10 adaptors suppress LPS-induced production of inflammatory cytokines. TNF-α (e), IL-6 (f), and IL-1β (g) quantified by ELISA in supernatants from human PBMCs stimulated for 24 h with LPS and 10 nM IL-10, IL-23, or IL-23 → IL-10 adaptors. n = 3 replicates per condition, N = 3. Bar graphs represent mean ± SD. Source data are provided as a Source data file.